When present, 3rd body effects in total joint replacement can obviate many of the wear rate improvements otherwise associated with advanced bearing materials such as highly cross-linked polyethylenes. While long recognized as a potential clinical concern, the difficulties of quantifying 3rd body challenge unfortunately have kept it largely confined to the domain of nebulous conjecture. Consequently, attempts to reduce the genesis of 3rd bodies and/or to study their effects on implant performance have been sporadic, heterogeneous, and often of questionable grounding in clinical realism. Building on a series of recent studies which have helped clarify the mechanisms linking 3rd body challenge, implant surface damage, and wear rate acceleration, two new directions of translational research are now proposed. The first of these directions is to quantify the 3rd body generation propensity of major intra-operative procedural steps of THA implantation surgery. Such data should be helpful to highlight the relative deleteriousness of specific procedural stages, a necessary initial step toward conceiving and documenting effective technical improvements. The second research direction is to establish a clinically-grounded framework for a practicable consensus protocol for laboratory 3rd body wear testing. To gain widespread acceptance, such a protocol will need to involve a reliably quantifiable 3rd body challenge that causes clinically realistic counterface damage. And, it will need to have the ability to reproducibly deliver wear rate accelerations in a clinically realistic range, ideally with a monotonic, mechanistically-grounded dose/response relationship. The proposed work will involve interdisciplinary collaboration among research groups at the University of Iowa, the University of Leeds, and Ohio State University. Peri-prosthetic tissue and fluid specimens will be obtained at various stages intra-operatively during patient surgeries and in cadaver preparations, from which specimens the 3rd body debris will be isolated and quantitatively analyzed. Computational models of 3rd body-induced wear rate acceleration will be extended to account for morphologically identifiable femoral head scratch damage, with direct validation physically. A registry of scratch damage on retrieval femoral heads in constructs with documented 3rd body challenge will be compiled using novel 3-dimensional laser micrometry, providing an objective basis to document clinically representative scratch damage regimens, and ranges of severity. A laboratory protocol will be refined to generate (registry-consistent) femoral head scratching from polyethylene-embedded 3rd body debris, with the damaged heads then being applied in standardized laboratory wear testing. At the conclusion of the proposed work, we expect to have identified which steps of THA surgical implantation are most problematic in terms of 3rd body debris generation. And, we expect to have developed a mechanistically-grounded protocol for laboratory simulation of 3rd body wear rate acceleration, suitable as a conceptual platform for a consensus testing standard. PUBLIC HEALTH RELEVANCE: In patients with total hip replacements, small particles comprised of hard materials such as metal, bone cement, or bone sometimes are unintentionally present in the tissues or fluid surrounding the implant, for reasons not well understood. These particles, known as 3rd bodies, can find their way into the ball-in-socket mechanism of the implant itself, where they roughen the otherwise very smooth bearing surfaces, causing the implant to rapidly wear, leading to clinical failure. It is important to find ways to minimize these 3rd body particles, and to develop implants that are more resistant to 3rd body damage.